Elizalde María Mercedes, Sevic Ina, González López Ledesma María Mora, Campos Rodolfo Héctor, Barbini Luciana, Flichman Diego Martin
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Virology. 2018 Jan 1;513:160-167. doi: 10.1016/j.virol.2017.10.016. Epub 2017 Nov 5.
In the context of pathogenesis of HBV infection, HBV genotypes and mutants have been shown to affect the natural course of chronic infection and treatment outcomes. In this work, we studied the induction of apoptosis by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. Both subgenotypes F1b and F4 HBV genome transfections induced cell death by apoptosis in human hepatocytes. The BCPdm (A1762T/G1764A) and preCore (G1896A) mutants induced higher levels of apoptosis than the wt virus. This increase in apoptosis was not associated with the enhanced viral replication of the variants. HBV-mediated apoptosis was independent of viral subgenotypes, and associated with the modulation of members of the regulatory Bcl-2 family proteins expression in the mitochondrial apoptotic pathway. Finally, the apoptosis induction increase observed for the preCore mutants suggests that HBeAg might have an anti-apoptotic effect in human hepatocytes.
在HBV感染的发病机制背景下，已表明HBV基因型和突变体可影响慢性感染的自然病程和治疗结果。在这项研究中，我们研究了HBV F1b和F4亚型以及自然发生的BCP和前核心突变体的复制对细胞凋亡的诱导作用。F1b和F4亚型HBV基因组转染均诱导人肝细胞发生凋亡导致细胞死亡。BCP双突变体（A1762T/G1764A）和前核心（G1896A）突变体诱导的细胞凋亡水平高于野生型病毒。这种凋亡增加与变异体病毒复制增强无关。HBV介导的细胞凋亡与病毒亚型无关，而与线粒体凋亡途径中调节性Bcl-2家族蛋白成员表达的调节有关。最后，前核心突变体观察到的凋亡诱导增加表明HBeAg可能在人肝细胞中具有抗凋亡作用。
